The objective of the research is to determine the mechanism by which membrane enzymes are regulated in aging and development. The approach is to study one constituent of the hepatic endoplasmic reticulum, the enzyme glucose-6-phosphatase. This enzyme seems to consist of two components, a carrier for glucose-6-P and a phosphohydrolase; the components are apparently regulated independently by corticosteroid and thyroid hormones. The response to the hormones changes as a function of age, and the mechanism is to be investigated. The carrier and phosphohydrolase will be purified to homogeneity and their structural organization in the membrane determined; the possible roles of protein synthesis, protein breakdown and activation of pre-existing molecules in the control of activity will be analyzed. Hepatocytes will be maintained in cell culture to determine whether the age-related changes are the result of alteration in the hepatocytes themselves, or their environment.